PHYSIOLOGICAL INHIBITORS OF HAEMOSTASIS IN HAEMOPHILIACS

Makris PE and Pithara E

Thrombosis and Haemostasis Unit , AHEPA University Hospital, Thessaloniki, GREECE.

The observation that haemophiliacs despite of the permanent deficiency of FVIII:C do not bleed continously led us to studying upon levels of physiological inhibitors of haemostasis.The aim of the study is to check upon the changes in the levels of certain coagulation factors as well as of all (except Heparin Coffactor II and HRGP), of physiological inhibitors of haemostasis during non-haemorrhagic periods. We 've examined a total of 67 persons, 15 of which were normal subjects (N),17 patients (pts) suffering from mild Willebrand disease (W) and 35 haemophiliacs A (H). During the study we 've made tests for: FVIII:C, FII:C, FVII:C, FXII:C, vWF,plasminogen (PLG) and Tissue Plasminogen Activators (TPA), inhibitors of coagulation as Antithrombin-III (AT-III), Protein C (PrC), inhibitrfibrinolysis such as Plasminogen Activator Inhibitors (PAI), and A2-Antiplasmin (A2-APL). All these tests were held while using the same blood sample and with the use of chromogenic substrate methods (CTS Behring).

Our results are shown on Table  (without standard deviations)

       FVIII  vWf    FII   FXII   PrC    AT-III   TPA    PLG   PAI   A2-APL   TAT

N    98.3   114.3  107  109.4   82.9    107.8     2.9     91.7    5.1      70.2        2.3

H      4.9   143.6    87    87.6   67.7      76.6     1.6    127.8   6.4      74.6        5.5

W   28.4      31.5    -      96.6   55.3      80.9     1.1    122.5   5.2      75.6        1.4

Considering as limit orienting thrombophilic tendency the X-3SD for PrC, AT-III, FXII, TPA, PLG or the X+3SD for PAI, A2-APL, vWF, we concluded that : there wasn't any patient who didn't have at least one or even more kinds of disturbances of the above factors.

HAEMOSTATIC  BALANCE IN HAEMOPHILIACS. A NEW APPROACH.

Pantelis  E  Makris, Elef  Pithara.

A' Med  Prop  Clinic, Thromb  &  Haem  Unit,Thessaloniki  54636,Greece.

Haemophiliacs,   despite  of  the  permanent   defeciency  of  FVIII:C,  do  not  bleed  continously .  Why is that  so?  Is there  another  haemostatic   balance  during  non  haemorragic   period  of  their  life, or  not?  These  questions  arise  from  the  random  findings  in  6  patients  suffering  from  von Willebrand  disease  which  were  found  to  have  a  decrease  in  Protein-C  levels  (<40%),  and  even more  by  the  observations   of  Makris  and  Pithara  (Fibrinolysis  1990; 4, Supl 1: 109)  on  the  PAI levels  of  haemophiliac   and  normal  persons.  The aim of  this  study  is  the  control  upon haemostatic   balance  during  non  haemorragic  periods  of  the  life  of  people  suffering  from hereditary  haemorragic   tendency.  We  examined  a  total  of  67  persons,  15  of  which  were  normal subjects  (NS), 17  patients   suffering   from   mild  von  Willebrand   disease  (vWD)  and  35 haemophiliacs   A, (H-A). During  the  study   we ' ve  made  tests  for:  FVIII:C,  FII:C,  FVII:C,  FXII:C, vWFVIII,  inhibitors  of  coagulation  as  Protein C,  PrC,  Antithrombin  III  (AT-III),  inhibitors  of fibrinolysis    such  as  Plasminogen   Activator  Inhibitors,  PAI , A₂ -Antiplasmin   (A₂ -APL)  and  also fibrinolysis    factors  as  plasminogen  (PLG)  and  tissue   plasminogen   activators  (TPA).  All  these tests  were   held   while   using   the   same   blood   sample  and  with  the  use  of  chromogen  substrate    methods ( Behring  Chromotimer    System ). Our  results   are  shown   on   table  1 *. *The  Standard   deviations   are  not  shown  in the table.

     FVIII  vWFVIII  FII   FXII  PrC   AT-III TPA   PLG  PAI  A₂-APL TAT*

NP   98.3    114.3   107  109.4  82.9  107.8  2.9   91.7  5.1  70.2  2.3

H-A   4.9    143.6    87   87.6  67.7   76.6  1.6  127.8  6.4  74.6  5.5

vWD  28.4     31.5    --   96.6  55.3   80.9  1.1  112.5  5.2  75.6  1.4

Considering   X-3S  for  PrC,  AT-III,  FXII,  TPA,  PLG  or  X+3S  for  PAI,  A₂-APL,  WFVIII  as  a  limit orienting  thrombophilic   tendency   we   concluded  that :  there   wasn' t   any   patient  who  didn' t  have at  least  on  or  even  more  kinds  of  disturbances   of  the  above  factors.  By  checking those  results   using   X²   we ' ve   come  up  with  a  very    significant   statisticaly   difference not  only   between  normal   subjects   and   haemophiliacs   (X²=8.5)   but   also  between   normal  subjects   and patients   suffering  from  von   Willebrand    disease  (X²= 4.85).

   As   a   result,  we  consider  that  patients  with   hereditary   haemorragic   tendency  develop certain   mechanisms   which   control  the   haemostatic    balance   and   protect  them   from   non provoked   haemorrages    during  non  haemorragic    periods  of  their  life.

MILD HAEMORRAGIC MANIFESTATIONS: HOW OFTEN ARE THEY?

Makris PE, Gerotjiafas G, Constantinidis C,Xanthopoulos V, Zdoukos T, Gerotjiafas A,MakrisS 

Thrombosis and Haemostasis Unit , AHEPA University Hospital, Thessaloniki, GREECE.

Research on the field of mild haemorragic tendency (eg. mild von Willebrand disease "vWD") as well as the assessment of their incidence in general population has been always an important goal for every relative laboratory.

For this reason we' ve studied the incidence of "vWD" by testing upon 1325 individuals for the following factors: a) Ristocetin Cofactor, RC, b) von Willebrand Factor Related Antigen "vWFR:Ag" and c) FVIII coagulant activity "FVIII:C".

Methods: i) for RC : a quantitative assessment based on the use of Aggregometer , ii) for vWFR:Ag : Laurel immunoelectrophoresis and iii) for FVIII:C a method using chromogenic substrate (CTS Behring).

Results: A) 214  persons (16.1 %)  referred mild haemorragic symptoms (rhinorrhagia, hematuria, menorrhagia, etc), B) 97 persons (7.3%) were found to have FVIII:C levels < 65 %, C) 55 persons (4.7 %) were found to have RC levels< 65 % , D) 60 persons (5.1 %) were found to have vWFR:Ag levels < 65 % and E) 32 persons (2.4 %) were found to have all three factors tested under our established limits.

Although our study is still on process it is obvious that mild haemorragic diseases are not very rare.